Periventricular diffusivity reflects APOE ε4–modulated amyloid accumulation and cognitive impairment in the Alzheimer's disease continuum

An automated method for quantifying periventricular diffusivity (PVeD) is developed. Lower PVeD is associated with higher amyloid load only in a mild cognitive impairment-dominant cohort. Higher amyloid burden may mediate the link between lower PVeD and poorer cognitive outcomes in the clinical cohort. Apolipoprotein E ε4 carriers show a reproducibly stronger inverse PVeD-amyloid association than non-carriers. Baseline PVeD can predict longitudinal Mini-Mental State Examination decline in two independent cohorts.